Jeremy A. Falk

Cardiac disease in chronic obstructive pulmonary disease.

The cardiac manifestations of chronic obstructive pulmonary disease (COPD) are numerous. Impairments of right ventricular dysfunction and pulmonary vascular disease are well known to complicate the clinical course of COPD and correlate inversely with survival. The pathogenesis of pulmonary vascular disease in COPD is likely multifactorial and related to alterations in gas exchange and vascular biology, as well as structural changes of the pulmonary vasculature and mechanical factors. Several modalities currently exist for the assessment of pulmonary vascular disease in COPD, but right heart catheterization remains the gold standard. Although no specific therapy other than oxygen has been generally accepted for the treatment of pulmonary hypertension in this population, there has been renewed interest in specific pulmonary vasodilators. The coexistence of COPD and coronary artery disease occurs frequently. This association is likely related to shared risk factors as well as similar pathogenic mechanisms, such as systemic inflammation. Management strategies for the care of patients with COPD and coronary artery disease are similar to those without COPD, but care must be given to address their respiratory limitations. Arrhythmias occur frequently in patients with COPD, but are rarely fatal and can generally be treated medically. Use of beta-blockers in the management of cardiac disease, while a theoretical concern in patients with increased airway resistance, is generally safe with the use of cardioselective agents.

Inhaled and Systemic Corticosteroids in Chronic Obstructive Pulmonary Disease

Systemic and local inflammation is central to the pathophysiology of chronic obstructive pulmonary disease (COPD). Increased levels of inflammation have been linked to a more progressive course in COPD and have been shown to be present during an exacerbation. Decreases in inflammatory cytokines, C-reactive protein, and inflammatory cells have been observed with corticosteroid use, suggesting a possible mechanism for a therapeutic benefit of steroids. No available data support the routine use of systemic corticosteroids in stable COPD; however, short courses during exacerbations are likely to improve length of hospitalization, lung function, and relapse rate. Inhaled corticosteroids (ICS) decrease the rate of exacerbation and may improve the response to bronchodilators and decrease dyspnea in stable COPD. No study shows that ICS reduce the loss of lung function; however, recent data suggest a possible survival benefit when combined with long-acting beta agonists. There are limited data on the use of ICS in the treatment of acute exacerbations of COPD, and its role in this setting must be more clearly defined. The empiric use of systemic corticosteroids perioperatively represents another area of uncertainty. The role of pharmacogenetics in the metabolism of corticosteroids in COPD is evolving but may be partially responsible for the observed variability in patient responsiveness. The potential benefits of systemic or inhaled corticosteroid use must be weighed against the risk of known toxicities.

Esophageal Motor Dysfunction and Gastroesophageal Reflux Are Prevalent in Lung Transplant Candidates

BACKGROUND Gastroesophageal reflux and aspiration contribute to the development of bronchiolitis obliterans and accelerate graft deterioration after lung transplantation (LTx). We evaluated LTx candidates for esophageal motor abnormalities and gastroesophageal reflux. METHODS Consecutive patients evaluated for LTx underwent 24-hour pH monitoring using a dual-channel pH probe and high-resolution esophageal manometry. High-resolution manometry was also performed in healthy control subjects. The prevalence of abnormal acid exposure was noted in the LTx candidates. RESULTS Thirty LTx candidates and 10 control subjects were evaluated. Lung transplantation candidates had higher residual upper and lower esophageal sphincter pressures. The mean proportion of peristaltic swallows was 21% lower in LTx candidates. Both hypotensive and aperistaltic swallows were sixfold more prevalent in LTx candidates than in control subjects. All control subjects had normal high-resolution manometry whereas 23 LTx candidates (76.7%) had esophageal peristaltic dysfunction. Abnormal acid exposure time was seen in the proximal and distal esophagus in 25% and 36% of LTx candidates, respectively. Lung transplantation candidates with idiopathic pulmonary fibrosis had more aperistaltic contractions, more negative minimum intrathoracic pressure, and a higher frequency of abnormal distal esophagus acid exposure. The majority of patients with complications after LTx demonstrated motor, anatomic, or pH abnormalities. CONCLUSIONS Disordered esophageal motor function and gastroesophageal reflux are common in LTx candidates. We believe high-resolution esophageal manometry is a valid tool to use and the abnormalities we identified may be representative of this unique patient population. The role of this study in predicting a worse outcome should be further studied in patients after LTx.

Overview of the Perioperative Management of Lung Volume Reduction Surgery Patients

This article reviews management strategies that may improve the outcome of thoracic surgery and particularly lung volume reduction surgery (LVRS) in patients with severe emphysema. Maximal preoperative pharmacologic therapy includes bronchodilators and inhaled corticosteroids to attain peak lung function at the time of surgery. Nonpharmacologic measures include smoking cessation and pulmonary rehabilitation. Mechanical ventilation during the perioperative period should ensure adequate oxygenation, while avoiding dynamic hyperinflation. Keys to successful postoperative care include close monitoring while in the intensive care unit, early extubation, adequate pain control, chest physiotherapy and appropriate chest tube management. Aggressive management of early postoperative complications, including air leaks, respiratory failure, arrhythmias, and hemorrhage, can also be expected to improve outcomes.

The inspiratory capacity/total lung capacity ratio as a predictor of survival in an emphysematous phenotype of chronic obstructive pulmonary disease

Background Forced expiratory volume in 1 second (FEV1) grades severity of COPD and predicts survival. We hypothesize that the inspiratory capacity/total lung capacity (IC/TLC) ratio, a sensitive measure of static lung hyperinflation, may have a significant association with survival in an emphysematous phenotype of COPD. Objectives To access the association between IC/TLC and survival in an emphysematous phenotype of COPD. Methods We performed a retrospective analysis of a large pulmonary function (PF) database with 39,050 entries, from April 1978 to October 2009. Emphysematous COPD was defined as reduced FEV1/forced vital capacity (FVC), increased TLC, and reduced diffusing capacity of the lungs for carbon monoxide (DLCO; beyond 95% confidence intervals [CIs]). We evaluated the association between survival in emphysematous COPD patients and the IC/TLC ratio evaluated both as dichotomous (≤25% vs >25%) and continuous predictors. Five hundred and ninety-six patients had reported death dates. Results Univariate analysis revealed that IC/TLC ≤25% was a significant predictor of death (hazard ratio [HR]: 2.39, P<0.0001). Median survivals were respectively 4.3 (95% CI: 3.8–4.9) and 11.9 years (95% CI: 10.3–13.2). Multivariable analysis revealed age (HR: 1.19, 95% CI: 1.14–1.24), female sex (HR: 0.69, 95% CI: 0.60–0.83), and IC/TLC ≤25% (HR: 1.69, 95% CI: 1.34–2.13) were related to the risk of death. Univariate analysis showed that continuous IC/TLC was associated with death, with an HR of 1.66 (95% CI: 1.52–1.81) for a 10% decrease in IC/TLC. Conclusion Adjusting for age and sex, IC/TLC ≤25% is related to increased risk of death, and IC/TLC as a continuum, is a significant predictor of mortality in emphysematous COPD patients.

Transplant patient with skin nodules.

MICROSCOPIC FINDINGS, CLINICAL COURSE, AND MANAGEMENT Hematoxylin and eosin (H/E)–stained tissue sections revealed edematous mucose with evidence of moderate acute and chronic inflammation and confluent areas of necrosis. Within the necrotic tissue were scattered double-walled wrinkled cystic structures and trophozoites measuring 13–20 mm, consistent with amebiasis. Rare trophozoites were identified within a vessel wall, indicative of angioinvasion. Gomori Methenamine silver (GMS) and periodic acid Schiff stains highlighted the cysts and trophozoites. Nearly a week after the sinus debridement, the patient developed multiple nodules on the bilateral proximal lower extremities. A punch biopsy of the skin nodules revealed focal tissue and fat necrosis with inflammatory debris but no amoebic organisms. Given the patient’s recent sinonasal findings and the presence of necrosis, a repeat biopsy of the skin lesions was recommended. This biopsy revealed scattered cysts and trophozoites predominantly within giant cells. For definitive speciation of the amoeba, formalin-fixed paraffin-embedded (FFPE) tissue sections were sent to Center for Disease Control and Prevention (CDC). Indirect immunofluorescent assay using specific anti-Acanthamoeba antibody confirmed the presence of Acanthamoeba (Fig. 1). A thorough investigation of the possible source of infection was performed. Although contaminated tap water was a possibility, no definitive source was identified. When the diagnosis of disseminated cutaneous acanthamoebiasis was made, the patient was started on a multidrug regimen with 5-flucytosine, azithromycin, bactrim, and pentamidine (intranasal). Concurrently, immunosuppressant drug levels were closely monitored with consequent decrease in their doses. The patient showed remarkable improvement, and the skin lesions gradually subsided. She was later discharged on azithromycin, bactrim, voriconazole, and miltefosine for 2 months and has no new lesions currently. As per the CDC recommendations, serology to determine baseline antibody titers, followed by monthly testing, was performed to monitor the patient.

Transplant patient with skin nodules. Acanthamoeba spp.

FIGURE 3. Sinonasal biopsy showing angioinvasion by the trophozoites (hematoxylin and eosin, ·10). From the Departments of *Pathology and Lab Medicine, †Microbiology, ‡Internal Medicine/Infectious Diseases, Cedars-Sinai Health Sciences, Los Angeles, CA; §Division of Parasitic Disease, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, GA; and ¶Department of Pulmonary Critical Care, Cedars-Sinai Health Sciences, Los Angeles, CA. The authors declare no conflicts of interest. Platform presentation at 49th annual meeting of American Society of Dermatopathology (ASDP) at Chicago, IL, October 2012. Reprints: Shivani Kandukuri, MBBS, MD, Department of Pathology and Lab Medicine, Cedars Sinai Medical Center, Pacific Theater Building, 116 North Robertson Boulevard 500, Los Angeles, CA 90048 (e-mail: shivani.kandukuri@cshs.org). Copyright

Low-Dose Valganciclovir for CMV Prophylaxis after Lung Transplantation

Purpose. Cytomegalovirus (CMV) remains an important pathogen following solid organ transplantation (SOT). Universal prophylaxis for CMV is adopted by most centers after lung transplantation. Various combinations studied for CMV prophylaxis include intravenous and oral ganciclovirs, oral valganciclovir, and CMV immunoglobulins. We present our experience with a low-dose of oral valganciclovir for CMV prophylaxis following lung transplantation. Methods and Materials. Our center started using 450 mg of daily oral valganciclovir for CMV prophylaxis in lung transplant recipients in Jan, 2001. A retrospective chart analysis of patients who underwent lung transplantation from January 2001 to December 2006 was done. Of 46 patients, 4 were excluded as they died within 30 days of transplant from postop complications. The mean age at transplant was 64 years, mostly single lung transplants (36/6) with a male-to-female ratio of 25/17. COPD was the most common reason for transplant (65%), and the serological CMV status of donors (D) and recipients (R) was as follows: D